WO2000032573A1

WO2000032573A1 - A meta-nitro phenol derivative and a process for producing it

Info

Publication number: WO2000032573A1
Application number: PCT/US1999/026016
Authority: WO
Inventors: Bai-Ping Ying; Sandeep Gupta; Masamitsu Tsukamoto; David A. Pulman; Takahiro Haga; Masahiko Ikeguchi
Original assignee: Ishihara Sangyo Kaisha, Ltd.
Priority date: 1998-11-30
Filing date: 1999-11-22
Publication date: 2000-06-08
Also published as: CN1376145A; EP1144380A4; JP2003506312A; WO2000032573A8; EP1144380A1; AU2145500A

Abstract

The present invention relates to a meta-nitro phenol derivative of formula (I) wherein X is halogen, cyano, nitro, C1-6haloalkyl or C1-6haloalkoxy; Y is hydrogen, halogen, cyano, nitro, C1-6haloalkyl or C1-6haloalkoxy; Z is oxygen, sulfur or NR; R is hydrogen or C1-6alkyl; Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C1-6alkylsulfonyl and C1-6haloalkylsulfonyl.

Description

A META-NITRO PHENOL DERIVATIVE AND A PROCESS FOR PRODUCING IT

The present invention relates to an intermediate for agricultural chemicals and a process for producing it.

BACKGROUND OF THE INVENTION

Certain herbicidal compounds and processes for their preparations are disclosed in WO98/ 1093 international patent publication. However, a meta-nitro phenol derivative of the present invention is not described therein.

There are some difficulties in a method of obtaining meta-nitro phenol derivatives from the corresponding phenols, because the OH group of phenols has an ortho-para directing effect in the nitration. Therefore, the nitration reaction of phenols must be carried out after the protection of the OH group with suitable protecting groups, such as alkoxycarbonyl, etc. Although meta-nitro phenol derivatives can be obtained by this method, it has the defect that the process is long and it is not suitable for an industrial process.

The present inventors have conducted an investigation for overcoming the defect in the method. As a result, the knowledge that the meta nitration reaction is allowed to proceed when the OH group of phenols is substituted by a specific substituent, was obtained.

SUMMARY OF THE INVENTION One aspect of the present invention is a meta-nitro phenol derivative of the formula (I):

(I) wherein X is halogen, cyano, Cl-6haloalkyl or Cl-6haloalkoxy; Y is hydrogen, halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Z is oxygen, sulfur or NR; R is hydrogen or Cl-6alkyl;

Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, Cl-6alkyl, Cl-6haloalkyl, Cl-6alkoxy, Cl-6haloalkoxy, Cl-6alkylsulfonyl and Cl-6haloalkylsulfonyl.

Another aspect of the present invention is a process for producing a meta-nitro phenol derivative of the formula (I) which comprises reacting a compound of the formula (II):

(ID wherein X, Y, Z and Ar are as defined above, with nitric acid.

DETAILED DESCRIPTION OF THE INVENTION In the above definitions, the term halogen indicates fluorine, chlorine, bromine or iodine. The term Cl-6haloalkyl or Cl-6haloalkoxy indicates Cl-6alkyl or Cl-6alkyl moiety partially or fully substituted with halogen atoms which may be same or different. The term Cl-6alkyl indicates either straight chain or branched alkyls containing 1-6 carbon atoms. The pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl represented by Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, Cl-6alkyl, Cl-6haloalkyl, Cl-6alkoxy, Cl- βhaloalkoxy, Cl-6alkylsulfonyl and Cl-6haloalkylsulfonyl. If there are two or more substituents on Ar, they may be the same or different. The meta-nitro phenol derivative of the present invention is preferably as follows:

(1) The compound of the formula (I) wherein X is halogen, Y is hydrogen, halogen or cyano and Z is oxygen. (2) The compound of the formula (I), wherein X is fluorine, Y is hydrogen or chlorine and Z is oxygen.

(3) The compound of the formula (I) wherein Ar is 2-pyridinyl or 2-pyrimidinyl in which the pyridinyl and the pyrimidinyl may be substituted with the substituent as defined above.

More preferred is the compound of the formula (I), wherein X is fluorine, Y is hydrogen or chlorine, Z is oxygen and Ar is 2-pyridinyl or 2-pyrimidinyl in which the pyridinyl and the pyrimidinyl may be substituted with the substituent as defined above. In the process for producing the meta-nitro phenol derivative of the formula (I), the nitration may be preformed either using fuming nitric acid alone or in acetic acid; or using nitric acid in the presence of sulfuric acid. In the process, the amount of nitric acid is usually from 1 to 4 moles ( preferably, 1.0 to 2.0 moles ) per one mole of the compound of the formula (II). The reaction is carried out between 0 to 30 °C. The reaction time is usually from

0.5 to 2 hours.

The compound of the formula (II) can be produced, for example, by the following method.

Ar-Hal

σo

In the above formulas, X, Y, Z and Ar are as defined above, Hal is halogen and R' is alkyl, phenyl or benzyl unsubstituted or substituted with halogen, alkyl, etc.

The reaction is conducted in the presence of a solvent and base. The solvent may, for example, be an aprotic polar solvent such as acetonitrile, methyl ethyl ketone, dimethylsulfoxide or N,N-dimethylforπιamide. The base may, for example, be an nlknli metal hydride such as sodium hydride or potassium hydride; an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; an alkali metal alkoxide such as sodium methoxide or sodium ethoxide; an alkali metal carbonate such as sodium carbonate or potassium carbonate; or a tertiary a ine such as triethylamine; or pyridine. The reaction temperature is usually from 0° to 250°C, preferably from 20° to 150°C. The reaction time is usually from 1 to 12 hours.

Among the compound of the formula (II), 2-(2-chloro-4-fluorophenoxy)pyrimidine or 2-(4-fluorophenoxy)pyrimidine are novel.

The compound of the formula (I) is useful as an intermediate for agricultural chemicals, especially for herbicidal compounds. A herbicidal compound can be prepared by the procedures as described in WO98/41093 from the compound of the formula (I) or the corresponding amino derivative. The compound of the formula (I) can be converted into the amino derivative.

reduction

(I) In the above formulas, X, Y, Z and Ar are as defined above. The reaction is conducted under typical reduction conditions such as treatment with iron, tin, tin [II] chloride or zinc in acetic acid or alcohoHc hydrochloric acid, or by hydrogenation using palladium on carbon, platinum dioxide, Raney Nickel, rhodium or ruthenium as catalyst.

Among the amino derivatives, those wherein Y is hydrogen, may be converted into the amino derivatives wherein Y is halogen.

^Hyγ^{x ' HaI}γγ^x

Z'^^NH, halogenation ^Z ^-^NH,

In the above formulas, X, Z and Ar are as defined above. Halogenation reaction can be carried out by reacting the starting compound with a halogenating agent such as N-chlorosuccinimide, sulfuryl chloride, or chlorine in a solvent in the presence or absence of a dehydrohalogenating agent at a temperature of 10 to 150°C for a period of 1-24 hours. The amount of halogenating agent and dehydrohalogenating agent may be respectively from 1-4 equivalents and from 0.001 to 1 equivalent to the starting compound. Examples of the solvent for the reaction are aliphatic hydrocarbons such as hexane, pentane; halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene; ethers such as diethyl ether, dioxane, tetrahydrofuran; esters such as ethyl acetate, butyl acetate; nitro compounds such as nitrobenzene; amides such as N,N-dimethylformamide; sulfur compound such as dimethylsulfoxide; amines such as pyridine, triethylamine; etc. These may be used as single solvents or in combination. As the dehydrohalogenating agent, either organic or inorganic bases can be used. These are exemplified by pyridine, triethylamine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc. After completion of the reaction, the product is isolated by ordinary post-treatment e.g. addition of water and extraction with an organic solvent. If necessary, product is purified by methods such as crystallization or chromatography.

The compound of the formula (I) can be produced, for example, by the following method.

In the above formulas, X, Y, Z and Ar are as defined above and G is halogen; alkyl sulfonyl which may be substituted by halogen or alkyl; phenyl sulfonyl which may be substituted by halogen or alkyl; benzyl sulfonyl which may be substituted by halogen or alkyl.

The reaction is conducted in the presence of a base. The base may, for example, be an alkah metal hydride such as sodium hydride or potassium hydride; an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; an alkah metal carbonate such as sodium carbonate or potassium carbonate; or pyridine.

The reaction is conducted, if necessary, in the presence of a solvent. The solvent may, for example, be a polar solvent such as dimethylsulfoxide, N,N- dimethylformamide or 1,3-άimethyl-imidazolinone; an aromatic solvent such as toluene, xylene or pyridine; an ethers such as tetrahydrofuran or dioxane. The reaction is preferably conducted in the presence of a catalyst, which increases the yield. The catalyst may, for example, be an alkali halide such as potassium iodide, potassium bromide or potassium chloride; a cuprous halide such as cuprous iodide, cuprous bromide or cuprous chloride; cupric halide such as cupric iodide, cupric bromide or cupric chloride; copper metal.

The reaction is conducted, if necessary, under an azeotropic distillation.

The reaction temperature is usually from 0 to 350°C, preferably from 100 to 200°C. The reaction time is usually from 1 to 12 hours.

The compound of the formula (III) can be produced, for example, by the following equation.

fluoroboration

(in) In the above formulas, X, Y, Z and Ar are as defined above. The reaction is conducted in the presence of solvents. The solvent may be an aprotic polar solvent such as diethyl ether, acetonitrile, methyl ethyl ketone, or dimethylsulfoxide and a protic solvent such as water, ethyl alcohol, or acetic acid. The mixed solvent of above solvents sometimes gives preferable results.

As the diazotizing agent are used various nitrites such as sodium nitrite, ethyl nitrite, or tert-but i nitrite.

The reaction temperature is usually from -10°C to 10°C, preferably from -5°C to 5°C. The reaction time is usually from 0.5 to 12 hours.

The compound of the formula (III) is the useful intermediate, which affords by the reaction with a certain (hetero)aromatic boronic acid according to the following equation, the herbicidal compounds (IV), that has the carbon-carbon linkage between the benzene ring and the (hetero)aromatic ring.

(III) (IV)

EXAMPLES The present invention will be further described in the following examples, but the present invention should not be construed as being limited thereto.

Example 1. Synthesis of 2-(2-chloro-4-fluorophenoxy)pyrimidine

2-Chloro-4-fluorophenol (6.0 g), 2-chloropyrimidine (5.3 g), and potassium carbonate (0.61 g) were mixed in methyl ethyl ketone (150 ml) and DMSO (50 ml) and heated at reflux temperature for four hours. The reaction mixture was partitioned between water and ethyl acetate, dried over sodium sulfate, evaporated to give the targeted compound (solid, 8.54 g, 93% yield). [*H NMR, CDCI3, δ 7.08 (2H, m), 7.25 (2H, m), 8.57 (2H, d, J = 4.8 Hz)ppm].

Example 2. Synthesis of 2-(2-cUoro-4-fluoro-5-nitrophenoxy)pyrimidine

2-(2-CUoro-4-fluorophenoxy)pyrimidine (7.0 g) was dissolved in H2SO4 (70 ml), HNO3 (4 ml) was added dropwise at room temperature and stirred for two hours. The reaction mixture was poured onto crushed ice and stirred for one hour (the final volume was 700 ml). The precipitate was collected by filtration, washed with water and dried in air to give 2-(2-cUoro-4-fluoro-5-nitrophenoxy)pyrimidine (6.17 g). The filtrate was neutralized with sodium hydroxide and extracted with ethyl acetate (100 ml) which was washed with water (50 ml) and evaporated to give an oil (0.39 g). The total yield was 78%. [*H NMR, CDCI3, δ 7.20 (1H, t, J = 4.8 Hz), 7.50 (1H, d, J = 10.0 Hz), 8.07 (1H, d, J = 6.9 Hz), 8.61 (2H, d, J = 4.8 Hz)ppm]. Similarly the following compounds were synthesized. 4-CMoro-2-(2-cUoro-4-fluoro-5-nitrophenox )pyrimidine [Η NMR, OMSO-de, δ 6.21 (1H, d, J = 7.0 Hz), 7.81 (1H, d, J = 10.5 Hz), 7.87 (1H, d, J = 6.9 Hz), 8.12 (1H, d, = 7.0 Hz)ppm].

6-Chloro-3-(2-chloro-4-fluoro-5-nitrophenoxy)pyridazine [^XH NMR, Acetone-ck, δ 7.54 (1H, d, J = 9.1 Hz), 7.63 (1H, d, J = 10.1 Hz), 7.78 (1H, d, J = 9.1 Hz), 8.16 (1H, d, J = 6.9 Hz)ppm].

3-Chloro-2-(2-chloro-4-fluoro-5-nitrophenoxy)pyrazine [*H NMR, DMSO-de, δ 8.04 (1H, d, J = 10.6 Hz), 8.16 (1H, d, J = 2.6 Hz), 8.29 (1H, d, J = 2.6 Hz), 8.40 (1H, d, J = 7.1 Hz)ppm].

6-Chloro-2-(2-chloro-4-fluoro-5-nitrophenoxy)pyrazine [Η NMR, DMSO-cfo δ 8.10 (1H, d, J = 10.6 Hz), 8.42 (1H, d, J = 6.9 Hz), 8.56 (1H, s), 8.69 (1H, s) ppm].

Example 3. Synthesis of 2-(2-chloro-4-fluoro-5-nitrophenoxy)pyrimidine

2-(2-Chloro-4-fluorophenoxy)pyrimidine (0.5 g) was slowly added to fuming nitric acid (2 ml) with stirring. The solution was stirred at ambient temperature for two hours and added to ice-water. The product was isolated by partitioning with ethyl acetate. The organic layer was washed with water, dried (anhydrous sodium sulfate) and evaporated to furnish the title compound (0.47 g, 78%).

Example 4. Synthesis of 2-(2-cUoro-4-fluoro-5-nitrophenoxy)pyrimidine Fuming nitric acid (20 ml) was added into a solution of 2-(2-chloro-4- fluorophenoxy)pyrimidine (1.0 g) in acetic acid (2ml). The solution was stirred at ambient temperature overnight. The reaction mixture was poured onto crushed ice.

The resulting precipitate was collected by filtration, washed with water, and dried in air to give a near white solid (0.75 g, 62% yield).

Example 5. Synthesis of 2-(5-amino-2-cHoro-4-fluorophenoxy)pyrimidine

Iron powder (6.79 g) was added to a solution of 2-(2-chloro-4-fluoro-5- nitrophenoxy)pyrimidine (6.56 g) in acetic acid (70 ml) and the resulting mixture was stirred at room temperature for 3 hours (monitored by TLC). The reaction mixture was diluted with ethyl acetate (200 ml), washed with water (100 ml), then saturated sodium chloride solution (50 ml) twice. The aqueous phase was extracted with ethyl acetate (100 ml). The ethyl acetate extract was washed with saturated sodium chloride (20 ml) twice. The ethyl acetate phases were combined, dried over sodium sulfate, and concentrated to 20 ml. The crystals were collected by filtration, washed with hexane-ethyl acetate (4:1), dried in air to give 2-(5-amino-2-chloro-4- fluorophenoxy)pyrimidine (5.36 g, 92 % yield). [*H NMR, CDC1₃, δ 6.69 (1H, d, J = 8.3 Hz), 7.06 (1H, t, J = 4.8 Hz), 7.10 (1H, d, J = 10.5 Hz), 8.56 (2H, d, J = 4.8 Hz)ppm].

Example 6. Synthesis of 2-(5-amino-2-chloro-4-fluorophenoxy)pyrimidine

Five-percent Palladium on carbon (0.02g, 4 wt. %) was added to an ethanol (5 ml) solution containing 2-(2-chloro-4-fluoro-5-nitrophenoxy)pyrimidine (0.5 g). The mixture was stirred under atmosphere of hydrogen at room temperature for 18 hrs. After the reaction was completed, the catalyst was filtered off and the solvent was evaporated to give 2 -(5-amino-2-chloro-4-fluorophenoxy)pyrimidine (0.43 g).

Example 7. Synthesis of 2-(5-amino-2-chloro-4-fluorophenoxy)pyrimidine

Platinum dioxide hydrated (0.06g, 3 wt. %), was added to an ethanol (40ml) solution containing 2-(2-ctøoro-4-fluoro-5-nitrophenoxy)pyrimidine (2.00g). The mixture was stirred under atmosphere of hydrogen at room temperature for 6 hrs.

After the reaction was completed, the catalyst was filtered off and the filtrate was evaporated to give crude product (1.83g). The crude product was chromatographed by silica gel (eluent, dichloromethane) to give pure 2-(5-amino-2-chloro-4-fluorophenoxy)- pyrimidine (1.61g).

Example 8. Synthesis of 4-chloro-2-fluoro-5-(2-pyrimidinyloxy)benzene diazonium fluoroborate

4-CUoro-2-fluoro-5-(2-pyrimid nyloxy)aniline (1.2 g (5 mmol)) was mixed

(exothermic) with fluoroboric acid (1.8 ml (55 %)) and water (0.75 ml) and was cooled to

-5 °C and treated with a solution of sodium nitrite (420 mg (6 mmol)) in water (2 ml).

The yellow 4-cWoro-2-fluoro-5-(2-p;yrimidinyloxy)benzene diazonium fluoroborate crystallized. After stirring for lhour it was filtered, washed with water and diethyl ether, and dried in vacuo. The yield was 0.6 g and the decomposing point was 188-90 o C.

Example 9. Synthesis of 2-(4-fluorophenoxy)pyrimidine

4-Fluorophenol (12.5 g), 2-chloropyrimidine (14.05 g), and potassium carbonate (18.47 g) were mixed in DMSO (125 ml) and the solution was stirred at 110°C for 2 hours. After cooling, the solution was added to water and the precipitate separated by filtration to afford the title compound ( 17.17 g, 81% yield). [Η NMR, CDC1₃, 7.0-7.21 (5H, m), 8.57 (2H, d, J = 4.8 Hz)ppm].

Example 10. Synthesis of 2-(4-fiuoro-3-nitrophenoxy)pyrimidine

2-(4-fluorophenoxy)pyrimidine (9.3 g) was dissolved in cone. H₂SO₄ (33.8 ml) and the solution stirred under ice cooling. Cone. HNO3 (3.4 ml) was added dropwise with stirring and the solution was allowed to stir at room temperature for 2 hours. The solution was added to ice-water and the product extracted with ethyl acetate. Trituration with ether furnished the title compound ( 8.05 g, 70% yield). [Η NMR, CDCI₃, 7.15 (1H, t, J = 4.8 Hz), 7.37 (1H, dd, J = 9.3 Hz), 7.52 (1H, m), 7.99 (1H, dd, J = 2.9, 6.2 Hz), 8.60 (2H, d, J = 4.8 Hz)ppm].

Example 11. Synthesis of 2-(3-amino-4-fluorophenoxy)pyrimidine

2-(4-Fluoro-3-nitrophenoxy)pyriιnidine (2.85 g) was dissolved in glacial acetic acid (121 ml) and iron powder (3.39 g) was slowly added in batches with stirring. The solution was stirred at room temperature for 12 hours under nitrogen. Water was added and product extracted with ethyl acetate. The organic layer was washed with water and brine. Evaporation afforded the title compound (1.86 g, 75 % yield). [^XH NMR, CDCI3, 5.30 (2H, br s), 6.28 (1H, m), 6.52 (1H, dd, J = 2.7, 7.7 Hz), 7.00 (1H, dd, J = 8.8, 11.1 Hz), 7.24 (1H, t, J = 4.7 Hz), 8.63 (2H, d, J = 4.7 Hz)ppm].

Example 12. Synthesis of 2-(5-amino-2-cMoro-4-fluorophenoxy)pyrimidine 2-(3-Amino-4-fluorophenoχy)pyrimi ine (0.5 g) was dissolved in anhydrous N,N- dimethylformamide (10 ml) and N-chlorosuccirjimide(0.33 g) was added. The solution was stirred at 80°C for 2 hours and water was added. The product was extracted with ethyl acetate and the organic layer was washed with water and brine followed by evaporation. The residue was crystallized from ether to afford the title compound (0.44 g, 75 % yield).

Example 13. Synthesis of 2-(5-amino-2-bromo-4-fluorophenoxy)pyrimidine

2-(3-Amino-4-fiuorophenoxy)pyrimidine (0.45 g) was dissolved in anhydrous N,N-dimethylformamide (10 ml) and N-bromosuccinimide (0.39 g) was added. The solution was stirred at 80°C for 2 hours and water was added. The product was extracted with ethyl acetate. The organic layer was washed with water and brine followed by evaporation. The product was purified by chromatography over silica gel (eluent, hexane:ethyl acetate, 6:4) to afford the title compound (0.41 g, 66 % yield). [Η NMR, acetone-d6, 5.07 (2H, br s), 6.80 (1H, d, J = 8.3 Hz), 7.21 (1H, t, J = 4.7 Hz), 7.29 (1H, d, J = 10.6 Hz), 8.59 (2H, d, J = 4.1 Hz)ppm].

Example 14. Synthesis of 2-Chloro-4-fluoro-5-nitrophenyl 2-pyrimidinyl ether

2-Chloro-4-fluoro-5-nitrophenol ( 1.98g ) was dissolved with dry tetrahydrofuran ( 10 ml ) and sodium hydride ( 42mg ) was added to it. The solvent was removed under a reduced pressure, followed by addition of potassium iodide ( 166mg ) as a catalyst and 2-cUoropyrimidine ( 1.27g ). The mixture was heated to 120°C for 3 hours and furthermore around 130°C for 1.5 hours. After cooling, ethyl acetate was added to it and the solution was filtered through celite by suction. The filtrate was washed with brine and 3 % aqueous potassium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed under a reduced pressure, giving brown oil. This oil was purified by chromatography over sihca gel ( eluent, dichloromethane ) to afford the title compound ( 1.69g, 63% yield ). Table I lists structures for some representative compounds of this invention.

TABLE I

No. X Ar

1 F Cl O 2-pyπmidinyl

2 Cl Cl o^" 2-pyπmidinyl 3 F Br 0 2-pyπmιdinyl

^~4 F CN ^~0 2-pyrimidinyl

F CF O 2-pyrimidinyl

6 F NO2 O 2-pyπmidinyl

^"7 OCHF2 O 2-pyrimidinyl ^~8 Cl O 4-chloro-2-pyπmidinyl

10 F Cl 0 ! 5-CF3-2-pyridinyl

11 F ^C1 i ⁰ i 3-pyridazinyl

12 F Cl 0 6-chloro-3-pyrida2inyl

13 F j Cl O 2-pyrazinyl

14 F Cl O 3-chloro-2-pyrazinyl

15 F Cl O 6-chloro-2-pyrazinyl

16 F Cl 0 4,6-dimethoxy-2-triazinyl

17 F Cl O 4,6-dimethyl-2-triεLzinyl

18 F Cl O 3-s-tetrazinyl

19 F Cl s 2-pyrimidinyl

20 F Cl NH 2-pyrimidinyl

20 F Cl NCHs 2-pyrimidinyl

21 F H O 2-pyrimidinyl

Claims

We claim:

1. A compound of the formula (I):

(I) wherein X is halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Y is hydrogen, halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy;

Z is oxygen, sulfur or NR; R is hydrogen or Cl-6alkyl;

2. The compound according to claim 1, wherein X is halogen, Y is hydrogen, halogen or cyano and Z is oxygen.

3. The compound according to claim 1, wherein X is fluorine, Y is hydrogen or chlorine and Z is oxygen.

4. The compound according to claim 1, wherein Ar is 2-pyridinyl or 2- pyrimidinyl in which the pyridinyl and the pyrimidinyl may be substituted with the substituent as defined in claim 1.

5. The compound according to claim 1, wherein X is fluorine, Y is hydrogen or chlorine, Z is oxygen and Ar is 2-pyridinyl or 2-pyrimidinyl in which the pyridinyl and the pyrimidinyl may be substituted with the substituent as defined in claim 1.

6. A process for producing a meta-nitro phenol derivative of the formula (I):

(D wherein X is halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Y is hydrogen, halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy;

Z is oxygen, sulfur or NR; R is hydrogen or Cl-6alkyl;

Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, Cl-6alkyl, Cl-6haloalkyl, Cl-6alkoxy, Cl-6haloalkoxy, Cl-6alkylsulfonyl and Cl-6haloalkylsulfonyl, which comprises reacting a compound of the formula (II):

(II) wherein X, Y, Z and Ar are as defined above, with nitric acid.

7. 2-(2-chloro-4-fluorophenoxy)pyrimidine or 2-(4-fluorophenoxy)-pyrimidine.

8. A process for producing a compound of the formula:

Ar._zΛ _NH2

wherein X is halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Hal is halogen; Z is oxygen, sulfur or NR; R is hydrogen or Cl-6alkyl;

Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, Cl-6alkyl, Cl-6haloalkyl, Cl-6alkoxy, Cl-6haloalkoxy, Cl-6alkylsulfonyl and Cl-6haloalkylsulfonyl, which comprises reacting a compound of the formula:

wherein X, Z and Ar are as defined above, with halogenating agent.

9. A compound of the formula (IH):

(HI) wherein X is halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy;

Y is hydrogen, halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Z is oxygen, sulfur or NR; R is hydrogen or Cl-6alkyl;

10. A process for producing a compound of the formula (III):

(HI) wherein X halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy;

Y is hydrogen, halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Z is oxygen, sulfur or NR; R is hydrogen or Cl-6alkyl; Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, Cl-6alkyl, Cl-6haloalkyl, Cl-6alkoxy, Cl-6haloalkoxy, Cl-6alkylsulfonyl and Cl-6haloalkylsulfonyl, which comprises reacting a compound of the formula:

wherein X, Y, Z and Ar are as defined above, with fluoroboric acid and diazotizing agent.

11. A process for producing an amino derivative, which comprises (1) undergoing a condensation reaction of a compound of the formula:

wherein X is halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy; Y is hydrogen, halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy;

Z is oxygen, sulfur or NR; and

R is hydrogen or Cl-6alkyl; and a compound of the formula: Ar-Hal or Ar-SO₂R' wherein Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, Cl-6alkyl, Cl-6haloalkyl, Cl-6alkoxy, Cl-6haloalkoxy, Cl-6alkylsulfonyl and Cl-6haloalkylsulfonyl; Hal is halogen; and

R' is alkyl, phenyl or benzyl in which R' may be substituted with at least one substituent selected from the group consisting of halogen and alkyl; to produce a compound of the formula (II):

(II) wherein X, Y, Z and Ar are as defined above,

(2) undergoing a nitration reaction of a compound of the formula (II) with nitric acid to produce a compound of the formula (I):

(D wherein X, Y, Z and Ar are as defined above, and (3) undergoing a reduction reaction of a compound of the formula (I) to produce a compound of the formula:

wherein X, Y, Z and Ar are as defined above.

12. A process for producing a meta-nitro phenol derivative of the formula (I):

(I) wherein X is halogen, cyano, nitro, Cl-6haloalkyl or Cl-6haloalkoxy;

^YTΎ^X wherein X, Y and Z are as defined above, with a compound of the formula:

Ar-G wherein Ar are as defined above and G is halogen; alkyl sulfonyl which may be substituted by halogen or alkyl; phenyl sulfonyl which may be substituted by halogen or alkyl; benzyl sulfonyl which may be substituted by halogen or alkyl.